tbuckley/cabot-search huggingface dataset:
Abstract P6-02-16: Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort
Authors: Florent HEGO, Maël BARTHOULOT, Charles PIERARD, Audrey Mailliez
Journal: Cancer Research (2023)

Abstract Background Studies evaluating prognostic impact of germline BRCA1/2 mutations (gBRCAm) on breast cancer patients reported controversial results. The primary aim of this study was to investigate outcomes of young gBRCAm patients with very early onset of breast cancer (&amp;lt; 30 years) compared with noncarriers. Methods In this retrospective study, 149 patients 30 years aged or younger at early breast cancer diagnosis between 2005 and 2019 were included in Oscar Lambret Center. Outcomes were overall survival (OS) and disease-free survival (DFS), defined as time from first diagnosis to first recurrence, second cancer or death from any cause, at 2 years, 5 years, and 10 years. Key patient data, kaplan-meier plots and outcomes were described by BRCA mutation status. Hazard ratios (HR) were calculated using Cox proportional-hazards models. Results Twenty-eight (18.8%) patients were gBRCAm carriers. The median follow-up was 6.5 years (IQR 0.25-16.5). Twenty-three deaths, 41 recurrences and 2 second cancers were reported. OS was 89.3% [70.4–96.4] in gBRCAm patients vs 99.1% [95% CI 93.9–99.9] in non-carriers patients at 2 years; 85.0% [64.7–94.1] vs 92.3% [85.1–96.1] at 5 years and 75.3% [52.5–88.3] vs 80.2% [66.6–88.7] at 10 years. There was no difference in OS between groups in multivariable analysis (HR=1.63 [0.55–4.77], p=0.37). Similar results were noted when comparing disease-free survival (HR=1.42 [0.64–3.11], p=0.38). Conclusions In this cohort of 149 patients with very early onset breast cancer, outcomes of gBRCAm mutation carriers did not differ from non-carriers when adjusted for others prognostic factors. Citation Format: Florent HEGO, Maël BARTHOULOT, Charles PIERARD, Audrey Mailliez. Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-16.
Abstract P4-05-07: Making Choices with Scarce Resources While Battling Breast Cancer In Nigeria
Authors: Gloria C. Okwu, Theodora O. Nwosu-Zita, Amina E. Haruna
Journal: Cancer Research (2023)

Abstract Background Breast cancer diagnosis in Nigeria is perceived by most as a death sentence and women who have been diagnosed have to battle with different choices at any given time, whether to fight so as to survive, what if they fight and lose, or maybe it is better not to fight at all judging from different cases discussed during our monthly cancer patient support group meetings. Making informed choices with limited resources is the bane of many breast cancer patients who feel guilty spending so much on their medical care while their family suffers financial neglect. This is because health insurance covers barely 10% of the country’s population and most families pays out of pocket. Some women on the other hand completely ignore their treatment and channel these resources towards education and general welfare of other members of their families. Aim To determine the extent to which financial choices made by women who are diagnosed and are undergoing treatment of breast cancer in Nigeria affects their treatment journey. Method A qualitative research approach was used and structural interview was used to collect data. Female breast cancer patient who are undergoing treatment and those who are through with their treatment {chemotherapy, surgery, and radiotherapy} and are currently on periodic check up with their oncologists participated in the study. Grounded theory was used in data analyses. Results Most of the patients interviewed had at one time or the other suspended their treatments in order to take care of pressing family issues and these had caused delays in proceeding with their treatment with its attendant consequences. Presentation Oral Presentation Citation Format: Gloria C. Okwu, Theodora O. Nwosu-Zita, Amina E. Haruna. Making Choices with Scarce Resources While Battling Breast Cancer In Nigeria [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-05-07.
Abstract P6-12-01: ALCAM (Activated Leukocyte Cell Adhesion Molecule) is associated with HGF/MET signalling pathway in different subtypes of breast cancer
Authors: Yiming Yang, Andrew J. Sanders, Wen G. Jiang
Journal: Cancer Research (2023)

Abstract Introduction. ALCAM (Activated Leukocyte Cell Adhesion Molecule), also known as CD166, is a cell adhesion molecule which belongs to the immunoglobulin superfamily and is widely expressed in various human tissues. It has been demonstrated that ALCAM plays an important role in the progression of malignant diseases and tumour metastasis in multiple cancer types including breast cancer. However, the molecular mechanism of ALCAM and cancer progression is currently unclear. The present study performed protein array analyses using ALCAM genetically manipulated cell models to select potential protein partners of ALCAM. The study focused on MET (Hepatocyte Growth Factor (HGF) Receptor), a prominent ALCAM interacting protein kinase and a protooncogene contributing to cancer progression and spread. Method. Human breast cancer cell lines MCF-7 and MDA-MB-231 were selected to create ALCAM knockdown cell models. A range of other breast cancer cell line with differing hormone receptor status were also used. Protein samples of transfected cells were used to perform Kinexus protein kinase microarray analysis. The protein interaction between ALCAM and other prospective protein kinases including MET was verified by the method of immunoprecipitation. Additionally, the ALCAM knockdown model was also assessed for the impact of ALCAM and HGF/MET on the biological functions by Electric Cell-substrate Impedance Sensing (ECIS). Results. MCF-7 and MDA MB-231 cells both were strongly expressed ALCAM. Cells models with ALCAM knocking down were successfully created by way of anti-ALCAM shRNA. We have shown on the protein kinase microarray analysis that the hepatocyte growth factor (HGF) receptor, MET was one of the kinases significantly affected following ALCAM knocking down. It was also found that the alteration of protein interaction between the MET protein kinase and ALCAM protein showed an opposite pattern between ER positive and ER negative ALCAM knocking down cells. This protein interaction was observed by immunoprecipitation in MDA-MB-361 and MDA-MB-231 cell lines, but not in MCF-7 cells. The biological analyses using the ECIS technologies showed that MET kinase inhibitors and exogenous recombinant HGF affected the ALCAM-mediated cell adhesion in different breast cancer subtypes. Conclusion. ALCAM is associated with HGF/MET signalling and the interaction between ALCAM and MET is different amongst subtypes of breast cancer which have different hormone receptor status. Citation Format: Yiming Yang, Andrew J. Sanders, Wen G. Jiang. ALCAM (Activated Leukocyte Cell Adhesion Molecule) is associated with HGF/MET signalling pathway in different subtypes of breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-12-01.
Abstract P2-26-08: Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent
Authors: Brijesh Kumar, Katie Batic, Poornima Bhat-Nakshatri, Maggie Granatir, Rebekah Addison, Megan Szymanski, Lee Ann Baldridge, Constance Temm, George Sandusky, Sandra Althouse, Anna Maria Storniolo, Harikrishna Nakshatri
Journal: Cancer Research (2023)

Abstract The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to the ductal epithelial cells in the normal breast of women of African Ancestry (AA) compared to European Ancestry (EA). By establishing and characterizing cell lines corresponding to these cells and validating in vitro findings with tissue microarrays of healthy breast tissue from AA, EA and Latina Ancestry (LA) women, we demonstrate that these cells have the properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFR. PROCR+/ZEB1+/PDGFR+ cells, hence renamed as PZP cells, are enriched in the normal breast tissues of AA compared to EA or LA women. In vitro, PZP cells trans-differentiated into adipocytes or osteocytes. In co-culture conditions, PZP:epithelial cell communication resulted in luminal epithelial cells acquiring basal/stem cell characteristics and increased expression of IL-6 suggesting the impact of this communication on the microenvironment and breast epithelial hierarchy. Consistent with this possibility, the level of phospho-STAT3, which is a downstream target of IL-6, was higher in the normal and cancerous breast tissues of AA compared to EA women. PZP cells transformed with HRasG12V ± SV40-T/t antigens generated metaplastic carcinoma in NSG mice suggesting that these cells could be the cell-of-origin of metaplastic breast cancers. Collectively, these results identify a stromal cell component that could influence the biology of breast cancer in AA women. Citation Format: Brijesh Kumar, Katie Batic, Poornima Bhat-Nakshatri, Maggie Granatir, Rebekah Addison, Megan Szymanski, Lee Ann Baldridge, Constance Temm, George Sandusky, Sandra Althouse, Anna Maria Storniolo, Harikrishna Nakshatri. Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-08.
Abstract OT3-33-01: Prospective, Multi-Center, Artificial Intelligence Study for Early Prediction of Serious Events under Treatment Is Now Open for Recruitment in Breast Cancer - OMCAT Trial in Progress
Authors: Timo Schinköthe, Christian Horst Tonk, Ronald Kates, Sherko Küemmel, Fatima Cardoso, Nadia Harbeck, Peter Staib, Annette Schmidt
Journal: Cancer Research (2023)

Abstract Background: Aim of the OMCAT trial (‘One Million CAncer Treatment months’, NCT04531995) is improvement of cancer patient care and safety by developing artificial intelligence (AI)-based, incident prediction algorithms. Incident detection allows early notification of treatment teams, enabling timely management changes or interventions. Ultimately the algorithms can also support improved health resource allocation. This trial in progress aims to provide learning databases in breast cancer comprising both electronic patient reported outcome (ePRO) data using the mobile medical device ‘CANKADO PRO-React’ and ground truth outcome data, which provide disease-specific events of interest (“incidents”) verified by the physician (e.g., during patient examinations). Methods: Incident prediction is posed as an application of stochastic time series analysis using AI and knowledge engineering technology. The learning process begins by fitting individualized and disease-specific stochastic process models to “incident-free” intervals extracted from the ePRO data series. Incidents produce detectable deviations from “ordinary” ePRO fluctuations. The algorithms are trained on CANKADO PRO-React data to produce real-time risk functions for predicting incidents on a clinically specified time horizon. Results: Considering the heterogeneity and combinatorics of diseases, stages, therapies, and types of events considered in this study, ultimately the AI algorithms aim to discover about 360 distinct predictive relationships. The estimate of one million treatment months is derived from statistical power analysis of this target, considering estimated median documentation time of six months per patient and estimated 400-500 patients per predictive relationship. To date, 45 centers in Germany have expressed interest in participating. This participation level will enable proof of principle. Ethics votes are already available in most regions. Other centers are invited to participate in this trial. Conclusions: OMCAT opens a whole new path towards evidence-trained AI and a novel combination of patient observation and predictive care. The goals of OMCAT are ambitious and will therefore require many more supporters. Citation Format: Timo Schinköthe, Christian Horst Tonk, Ronald Kates, Sherko Küemmel, Fatima Cardoso, Nadia Harbeck, Peter Staib, Annette Schmidt. Prospective, Multi-Center, Artificial Intelligence Study for Early Prediction of Serious Events under Treatment Is Now Open for Recruitment in Breast Cancer - OMCAT Trial in Progress [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-33-01.
Abstract P5-02-12: Prognostic relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy
Authors: Ying Zhou, Jinmei Zhou, Haoyuan Shi, Zhiyuan Hu, Yanlian Yang, Zefei Jiang, Tao Wang
Journal: Cancer Research (2023)

Abstract Rationale: Breast cancer has become the leading cause of cancer mortality in women. Although immune checkpoint inhibitors targeting programmed death-1 (PD-1) are promising, it remains unclear whether PD-L1 expression on circulating tumor cells (CTCs) has predictive and prognostic values in predict and stratify metastatic breast cancer (MBC) patients who can benefit from anti-PD-1 immunotherapy. Methods: Twenty six MBC patients that received anti-PD-1 immunotherapy were enrolled in this study. The peptide-based Pep@MNPs method was used to isolate and enumerate CTCs from 2.0 ml of peripheral venous blood. The expression of PD-L1 on CTCs was evaluated by an established immunoscoring system categorizing into four classes (negative, low, medium, and high). Results: Our data showed that 92.3% (24/26) of patients had CTCs, 83.3% (20/26) of patients had PD-L1-positive CTCs, and 65.4% (17/26) of patients had PD-L1-high CTCs. We revealed that the clinical benefit rate (CBR) of patients with a cut-off value of ≥ 35% PD-L1-high CTCs (66.6%) was higher than the others (29.4%). We indicated that PD-L1 expression on CTCs from MBC patients treated with anti-PD-1 monotherapy was dynamic. We demonstrated that MBC patients with a cut-off value of ≥ 35% PD-L1-high CTCs had longer PFS (P&amp;lt; 0.05) and OS (P&amp;lt; 0.01) compared with patients with a cut-off value of &amp;lt; 35% PD-L1-high CTCs. Conclusion: Our findings suggested that PD-L1 expression on CTCs could predict the therapeutic response and clinical outcomes, providing a valuable predictive and prognostic biomarker for patients treated with anti-PD-1 immunotherapy. Citation Format: Ying Zhou, Jinmei Zhou, Haoyuan Shi, Zhiyuan Hu, Yanlian Yang, Zefei Jiang, Tao Wang. Prognostic relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-12.
Abstract P4-07-63: Local delivery of immunotherapeutics as an in situ vaccine in triple negative breast cancer
Authors: Siena Mantooth, David Zaharoff
Journal: Cancer Research (2023)

Abstract Introduction. Breast cancer (BC) is among the most common types of cancer among women, with an estimated 287,850 new cases and 43,250 deaths in 2022 [1]. Triple negative breast cancer (TNBC), characterized by lack of ER/PR/HER2 receptors, constitutes 10-15% of diagnosed BC and correlates with the worst prognosis and most aggressive form of the disease [2]. Additionally, compared to the other BC subtypes, TNBC have higher rates of recurrence and highest therapy resistance [2]. Because TNBC lacks a clearly defined target, in situ vaccination may pose a viable therapy option, to locally stimulate an immune response and thereby reduce the tumor burden and prevent recurrence and metastasis. To this end, we developed an injectable delivery medium to effectively localize immune agonists at the site of the tumor. Materials and methods. Hydrogel delivery medium: Low-viscosity, high-deacetylated chitosan was crosslinked with 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide at room temperature overnight. The mixture was dialyzed and freeze-dried. A hydrogel was formed by dissolving the chitosan in deionized water at concentrations from 25-50 mg/mL. In vivo tumor treatment: 1e5 E0771 breast cancer cells were implanted subcutaneously in the right flank of C57BL/6 mice. When tumors were 50-100mm3, mice were treated intratumorally with 50ug Poly(I:C) + 50ug CpG in 30 mg/mL chitosan gel, with 50ug Poly(I:C) + 50ug CpG in saline, or with gel alone. In the second experiment, to enhance the anti-tumor effect of the immunotherapeutic, 2ug of the cytokine interleukin-12 in the chitosan gel will be delivered intratumorally. All experiments involving laboratory animals were approved by the Institutional Animal Care and Use Committee at North Carolina State University. Results and Discussion. The gel was effectively localized within the tumor environment upon injection. The localized Poly(I:C) + CpG in the gel demonstrated an enhanced anti-tumor effect, compared to gel alone. Ongoing work will determine the efficacy of administering the cytokine IL-12. Acknowledgements. This work is supported by an NSF Graduate Research Fellowship. References. [1] Siegel R, et al. CA A Cancer J Clin (2022) 72(1):7-33. [2] Retecki K, et al. Cancers (2021) 13(23):6012 Citation Format: Siena Mantooth, David Zaharoff. Local delivery of immunotherapeutics as an in situ vaccine in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-63.
Abstract P1-05-36: AI-Based Smartphone App Using a Single-Lead ECG for Automated QTc Diagnostics in Oncology
Authors: Timo Schinköthe, Christian Horst Tonk, Nadia Harbeck, Vanda Carmelo, Joana Gomes Feliciano, Rachel Wuerstlein, Sherko Küemmel, Annette Schmidt
Journal: Cancer Research (2023)

Abstract Introduction: Long QT syndrome is a common cardiotoxic side effect of various anti-tumor drugs. Previous cardiological monitoring of oncological patients is primarily complex and requires for non-internal oncologists a consultation. Therefore, the QTc-Tracker smartphone APP was developed, which enabled a tele-cardiological diagnosis of the QTc time with standard single-lead ECG devices. As a result, diagnosis times could already be reduced by 99%. The further development examined an automatic determination of the QT time using the smartphone APP. However, since single-lead ECG devices are significantly more susceptible to interference, the determination of the QT time is more complex than with 12-lead ECGs. Methods: The QTc-Tracker smartphone APP was developed to determine the QT time. Self-tracker single-lead ECG devices were used to record the lead I signal. The ECG recordings were analyzed in the APP and passed on to an external cardiologist as reference. The APP used artificial intelligence and was trained in the first phase and validated in the second phase. The first phase aimed to improve QT time detection. The results of the APP were compared with the findings of the external cardiologist. In both phases, ECGs from breast cancer patients receiving ribociclib were used. Results: A total of 1889 single-lead ECGs were carried out. 248 of these could not be evaluated (13%). QTc prolongation, according to CTCAE, was diagnosed in 41 cases (2.5%). 878 of the evaluable ECGs were used for the training phase and 763 for the evaluation phase. In the first group (before the improvement), the sensitivity to automatically detect a prolongation of the QT time was 36%, and the specificity was 96%. In the evaluation collective (after the training), the sensitivity went up to 85%, and the specificity was unchanged at 96%. Conclusions: The trained method of the QTc tracker is able to reliably detect a QT time lengthening even without a cardiological diagnosis only by using single-lead self-tracker ECG’s. In the rare cases in which an elongation was not detected, the cardiac diagnosis was only a few milliseconds above the threshold value. This artificial intelligence-based smartphone APP is not intended to replace the cardiological diagnosis, but it can simplify routine processes and help to decide which patients need a cardiological examination more urgently. Citation Format: Timo Schinköthe, Christian Horst Tonk, Nadia Harbeck, Vanda Carmelo, Joana Gomes Feliciano, Rachel Wuerstlein, Sherko Küemmel, Annette Schmidt. AI-Based Smartphone App Using a Single-Lead ECG for Automated QTc Diagnostics in Oncology [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-36.